Amino Acids

L-Theanine

Scientific Name:
L-gamma-glutamylethylamide

L-theanine is a calming amino acid that naturally occurs in green tea. It is used as a nootropic because it supports focused attention, mental alertness, and a calm, relaxed sense of mental energy. L-theanine is often used with caffeine in nootropic stacks, because the combination supports task switching, accuracy, and focus. L-theanine promotes alpha brain waves (α-waves), which are thought of as a marker of relaxation [1]. This brain state also reduces the perception of stress. L-theanine has a few other lesser-known functional actions. L-theanine can be broken down into glutamate, which is a building block for glutamatergic signaling (i.e., the glutamate-GABA pathway) and for glutathione, an antioxidant used for detoxification. And L-theanine, because of another metabolite, primes specialized immune cells—gamma delta T cells—that help the immune system respond more efficiently to new antigens and have enhanced immune memory.* The best dietary sources of L-theanine are green and black tea (made from Camellia sinensis): L-theanine comprises up to 50% of total amino acids in tea leaves.

TOP BENEFITS OF L-THEANINE

Supports cognitive function*

Supports relaxed mood*

Supports stress resilience*

Supports sleep*

Supports general immune health*

QUALIA’S L-THEANINE SOURCING

L-theanine is non-GMO, gluten-free, and vegan.

L-THEANINE FORMULATING PRINCIPLES AND RATIONALE

L-theanine has been studied clinically over a fairly wide range of servings, with the most common range being 100-400 mg. Evidence suggests a threshold response (see Qualia Dosing Principles) when L-theanine is given by itself (i.e., much of the benefits occur within the lower end of the serving range). That said, the serving of L-theanine used in a Qualia formulation can vary significantly depending upon what other ingredients it’s combined with and the intent of the formulation. Qualia looks for additive or complementary ingredient combinations. In some cases, ingredients tend to be most complementary when used at certain ratios. L-theanine falls into this category. As an example, when used as part of a nootropic formula combined with a source of caffeine, the serving of L-theanine might be chosen to provide about double the amount of caffeine and/or theobromine (i.e., ~2:1 ratio). But when used in combination with GABA before bedtime for supporting sleep, the serving might be as little as 20% of the GABA amount (i.e., 1:5 ratio). Following oral intake, the amount of L-theanine in the brain increase within the first hour (i.e., it’s able to cross the blood-brain barrier [2], so in general, L-Theanine has a fairly quick onset and is often experienced within 30-45 minutes of taking it.*

L-THEANINE KEY MECHANISMS

Supports brain function*

Supports attention* [3–5]

Supports memory and learning* [4–7]

Supports executive function* [4,8]

Supports faster reaction times* [3]

Supports alpha (α) brain waves (α-waves are associated with relaxation, selective attention, and mental alertness)* [1,3,9–12]

Supports hippocampal activity* [13]

Supports dopamine signaling* [14–20]

Supports serotonin signaling* [20]

Supports GABA signaling* [20]

Binds to glutamate receptors (with low affinity)* [21–23]

Supports hippocampal neurogenesis (in animals)* [6]

Supports brain-derived neurotrophic factor (BDNF) levels* [6,23,24] 

Supports neuroprotective functions* [7,25–28]

Supports healthy mood and stress responses*

Supports a calm/relaxed mood* [4,8,12,13,25,29–32]

Supports a positive mental-emotional bias* [4,8]

Supports psychological and physiological stress responses* [33]

Supports healthy behavioral and cognitive responses to stress* [26,34]

Reduces fight or flight nervous system activity (i.e., promotes relaxation response)* [33]

Supports sleep*

Supports sleep efficiency and quality* [4,8,35,36]

Counters some of caffeine’s effects on deep sleep* [37]

Supports healthy immune function*

Supports general immune health* [38–40]

Supports post-exercise immunity* [41–44]

Supports innate immunity* [42,45,46]

Supports adaptive immunity* [42,46,47]

Supports immune signaling* [42,48]

Supports healthy immune cell function [41–46,49–54]

Supports healthy gastrointestinal function*

Supports a healthy gut microbiota* [55]

Supports amino acid absorption* [56]

Complementary ingredients*

Caffeine for cognitive performance* [57–60]

GABA for supporting sleep quality* [61]

L-Cysteine in support of general immune health* [38,41,43,44,50,53,62]

Green tea extracts in support of general immune health* [39,40]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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L-Ornithine (as L-Ornithine Hydrochloride)

L-Ornithine is an amino acid. It is found in the diet and can be produced in the human body, with the combination determining body stores. Meats, nuts, rice, eggs, fish, soybeans and dairy are the best food sources. Ornithine can be taken up by the brain and is found in many other tissues, with its highest concentrations found in connective tissues, such as the skin. L-ornithine is a precursor for the synthesis of L-proline, which is one of the primary amino acids in collagen, the main structural components of connective tissues. It is also involved in the urea cycle, which is important for the removal of excess nitrogen compounds such as ammonia—these can be fatigue-causing metabolites in active tissues, like the brain and muscles—and in the synthesis of polyamines, which are involved in cell growth and tissue healing. L-ornithine is able to influence a number of brain functions, including hypothalamic-pituitary-adrenal (HPA) axis signaling, as well as GABA and glutamate pathways, for example.*

TOP BENEFITS OF L-ORNITHINE

Supports brain function *

Supports skin health *

Supports a healthy stress response *

QUALIA’S L-ORNITHINE SOURCING

L-Ornithine Hydrochloride is non-GMO, gluten-free, and vegan.

L-ORNITHINE FORMULATING PRINCIPLES AND RATIONALE

L-ornithine has been used in clinical studies at doses ranging from 200 mg to a few grams. The most common dose, when given alone in recent human studies, has been 400 mg a day. L-ornithine has been complementary with caffeine at a dose of 200 mg L-ornithine in combination with 100 mg caffeine [1]. Based on our review of the research, Qualia believes L-ornithine follows a threshold response (see Qualia Dosing Principles) when given to healthy people, which means we expect the majority of functional benefits to occur within the 200-400 mg range. We recommend a serving of L-ornithine within this studied range when it is combined with caffeine and used as a nootropic (to be consistent with the human study); however, we may recommend a lower serving if L-ornithine is being used in a formula to augment dietary intake).*

L-ORNITHINE KEY MECHANISMS

Supports healthy brain function* 

Influences the hypothalamic-pituitary-adrenal (HPA) axis* [2,3]

Supports regulation of growth hormone signaling* [3–5]

Supports healthy behavioral responses to stress* [2,6]

Promotes healthy levels of stress signaling molecules* [2,3,5,7–9]

Supports sleep* [7,10,11]

Promotes healthy melatonin signaling* [5,12]

Supports brain metabolism, oxygen utilization, and neutralization of ammonia* [13–16]

Metabolic precursor for GABA and glutamate neurotransmitter pathways* [17–22]

Supports brain protein synthesis* [23–26]

Promotes skin health*

Supports skin levels of collagen-constituting amino acids* [27]

Supports collagen deposition* [28]

Supports wound repair functions* [28]

Enhances ergogenic actions*

Supports maximal anaerobic exercise performance* [29]

Supports resistance to physical fatigue* [30]

Complementary ingredients*

Caffeine in supporting mood and concentration* [1]

Caffeine in influencing the levels of stress hormone* [1]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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Acetyl-L-Carnitine

Acetyl-L-Carnitine (ALCAR) is an acetylated form of L-carnitine. The major difference between ALCAR and L-carnitine is that ALCAR more readily crosses the blood-brain barrier, which is why it tends to be the preferred form for use in brain and nervous system support. The bioavailability of ALCAR is thought to be higher than that of L-carnitine. The name carnitine is derived from Latin “carnus” (flesh) because it was originally found in meat extracts. Adults eating animal products consume about 60–180 milligrams of carnitine per day ^[1]. Vegans get noticeably less (about 10–12 milligrams) [1], with vegetarians getting a bit more than vegans because of eating dairy products. The carnitine in ALCAR and L-carnitine support the same functions. The most important role of carnitine is in mitochondrial fat metabolism—it is used to transport long-chain fatty acids across the mitochondrial membrane for breakdown by mitochondrial β-oxidation. This transportation function allows fats and oils from our diet to be used for energy production and enhances mitochondrial potential to burn fat. Unlike L-carnitine, which does not contain an acetyl group, ALCAR can support acetylcholine synthesis, because the acetyl group in ALCAR can be delivered to coenzyme A to yield acetyl-CoA, which in turn can be used for the synthesis of the neurotransmitter acetylcholine. Acetyl-CoA can also be used for cell energy production as it is the primary substrate for the Krebs cycle in mitochondria, essential for the production of ATP. Accordingly, ALCAR has been shown to enhance cholinergic neurotransmission and support brain energy metabolism in several studies; it has also shown significant neuroprotective effects [2–5].*

TOP BENEFITS OF ACETYL-L-CARNITINE

Supports brain function *

Supports mood *

Supports energy metabolism *

Supports healthy aging *

QUALIA’S ACETYL-L-CARNITINE SOURCING

ALCAR supplies carnitine, which is used by the body to transport long-chain fatty acids (fats) so they can be broken down and used to make cellular energy (ATP). It is also a source of acetyl groups that can be used to make acetylCoA. 

While ALCAR and L-carnitine support the same mitochondrial functions, the ALCAR form tends to be preferentially used in research for brain and nervous system support.

ALCAR is NON-GMO and vegan.

ACETYL-L-CARNITINE FORMULATING PRINCIPLES AND RATIONALE

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L-Carnitine

L-carnitine is an important molecule because it’s needed to convert fat into energy. The name carnitine is derived from Latin “carnus” (flesh), because it was originally found in meat extracts. Animal products such as meat, poultry, fish, and milk are the best food sources, with redder meats tending to have higher levels of L-carnitine. Adults eating animal products consume about 60–180 milligrams of carnitine per day.[1] The human body can make carnitine from lysine using other micronutrients as cofactors. Adults eating a variety of animal products get about 75% of the daily carnitine needs filled from the diet, so only need to make about 25% of what they use.[2] Vegans get noticeably less (about 10–12 milligrams),[1] with vegetarians getting a bit more than vegans because of eating dairy products. In both cases, because the diet is limited in L-carnitine, they may need to make as much as 90% of their daily needs.[2] While the human body can make carnitine from lysine, it may not always be able to make sufficient amounts to meet demands. This has led to it being thought of as a “conditionally essential” nutrient. L-carnitine’s most important role is in mitochondrial fat metabolism—it is used to transport long-chain fatty acids across the mitochondrial membrane for breakdown by mitochondrial β-oxidation. This transportation function allows fats and oils from our diet to be used for energy production and enhances mitochondria’s potential to burn fat. This function is especially important in tissues and organs that use a lot of fat as an energy source, including the heart and skeletal muscles.*

Top Benefits of L-carnitine

Supports healthy mitochondrial function *

Supports joint health *

Supports healthy aging *

Qualia’s L-carnitine Sourcing

Carnitine can be supplemented as either L-carnitine or acetyl-L-carnitine (ALCAR). While ALCAR and L-carnitine support the same functions, in general, the ALCAR form tends to be used in research more for brain and nervous system support, while the L-carnitine form has been researched more for supporting the healthy function of heart and skeletal muscles. But both forms support all tissues.*

L-carnitine sourcing is a non-GMO, gluten-free, and vegan ingredient.

L-carnitine Formulating Principles and Rationale

L-carnitine is generally considered to be dose-dependent (see Qualia Formulating Principles) in the range it’s commonly supplemented (between 1000 mg to several grams a day) when given alone. These amounts are higher than what the body gets from the diet and makes daily, while a lower serving (250-500 mg) could be obtained from a diet rich in foods that are good sources of L-carnitine. We supplement L-carnitine in this latter, lower range to help support a more optimal dietary intake.*

L-carnitine Key Mechanisms

Supports mitochondrial function and structure*

Supports healthy mitochondrial function and structure* [3,4]

Supports fatty acid β-oxidation* [5]

Promotes the healthy production of ATP* [4]

Supports joint health*

Supports joint comfort* [6–8]

Supports joint structure and function maintenance* [8–12]

Supports synovial membrane and fluid health* [13]

Supports healthy joint immune mediator levels* [9]

Healthy aging and general well-being*

Supports healthy cardiovascular function* [14–16]

Supports balanced reactive oxygen species (ROS) production and oxidative stress* [3,17]

Supports neuroprotective functions* [3]

Supports telomerase activity and telomere length* [18,19]

Supports mesenchymal stem cell longevity* [18–20]

Supports healthy immune signaling* [7]

Complementary ingredients*

Lipoic acid – supports  mitochondrial function* [21]

Creatine and L-leucine – support healthy muscle function and structure* [22]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

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Taurine

Scientific Name:
2-aminoethanesulphonic acid

L-Tryptophan

L-Tryptophan is an essential amino acid. The body cannot synthesize it: it must be obtained from the diet. It’s been known for decades that L-tryptophan has niacin equivalent activity in the body (i.e., we can make the NAD+ molecules from it). L-tryptophan is unique because it’s the only way to build NAD+ that doesn’t start from one of the older or newer vitamin B3’s. L-tryptophan does this by a de novo synthesis pathway, which creates a niacin molecule through a series of biological reactions (many other important molecules are also created in this process). In the morning, most L-tryptophan—as much as 95%—is used in this pathway. L-tryptophan has enhanced aspects of exercise performance when taken before working out, presumably because of this role in cellular energy production. At night, while most L-tryptophan is still funneled into the de novo pathway, relatively more gets directed to a different pathway, 5-hydroxytryptophan (5-HTP) → serotonin → melatonin. This alternate pathway is involved in regulating sleep-wake cycles and nighttime body clock functions. This alternate pathway might be why low-to-moderate doses of L-tryptophan supports skills that fall into the social cognitive domain: these include prosocial behaviors like cooperation, empathy, getting along with others, and altruism. Since this alternate pathway can be used to make the neurohormone melatonin, L-tryptophan has been used to support healthier sleep cycles. Giving extra L-tryptophan allows the body to use it where it is needed most over the next 12-16 hours. In general, giving extra L-tryptophan with breakfast supports both daytime mood (presumably via supporting serotonin function) and nightly sleep (presumably via supporting melatonin function). Giving some extra L-tryptophan early in the day also helps support the body clock, orienting many of its daytime functions earlier in the day. L-tryptophan supplementation may support prosocial behaviors. Low-to-modest doses of L-tryptophan in the evening may support healthier sleep cycles.*

Top Benefits of L-Tryptophan

Supports cell energy generation *

Supports healthy aging *

Supports healthy sleep*

Supports mood *

Supports prosocial behaviors *

Qualia’s L-Tryptophan Sourcing

L-Tryptophan is used as a precursor (i.e., substrate) by the body to make NAD, serotonin, and melatonin. Our main reason for including it in a formulation would be to support biosynthesis of one or more of these important molecules.

In general, L-tryptophan is additive with other strategies for making NAD (such as the non-flushing form (niacinamide) and flushing form (niacin) of vitamin B3, so it can be useful to stack the two together in formulations.

L-Tryptophan sourcing is focused on identifying and purchasing from a reputable supplier and ensuring it is NON-GMO, gluten-free and vegan.

L-Tryptophan Formulating Principles and Rationale

One of our formulating principles is to determine whether there is a serving range, in which many of the benefits occur and above which there appears to be diminishing returns (i.e., a threshold), and to provide a serving within this threshold range (see Qualia Dosing Principles). We consider L-tryptophan to be one of these threshold compounds, because many of the benefits appear to occur at a low amount, and in some functional areas a worse response may occur at higher amounts. As an example, in a comparative study for sleep, the lowest amount used produced a healthier deep sleep response than the higher amount [1]. It’s been estimated that an average adult diet provides about 800-1000 mg/day of L-tryptophan. In studies that have looked at augmenting the breakfast meal with L-tryptophan, amounts lower than that in an average diet have been sufficient to produce positive subjective responses during the day, with sleep that night, and with overall body clock function. These studies are consistent with L-tryptophan supplementation supporting healthier function when given in amounts that are less than what would be found in an average diet.*

L-Tryptophan Key Mechanisms

NAD(P) synthesis*

L-tryptophan is a substrate in the de novo NAD+ synthesis pathway via the kynurenine pathway (KP)* [2]

NAD+ can be converted to the coenzyme NADP+ by the enzyme NAD kinase* [3]

NAD(H) and NADP(H) are key molecules in essential redox pathways of cellular metabolism and energy production* [4]

NAD(H) is essential for the production of ATP through the citric acid cycle and oxidative phosphorylation* [4]

NADP(H) is essential in many anabolic metabolic reactions, including DNA and RNA synthesis* [4]

NADP(H) is a cofactor for some cytochrome P450 enzymes that detoxify xenobiotics* [5]

NADPH also acts as a cofactor for glutathione reductase, the enzyme used to maintain reduced glutathione (GSH) levels* [4]

NAD(H) and NADP(H) are essential for healthy aging* [4]

Supports brain function*

L-tryptophan is a precursor for serotonin (a neurotransmitter) and melatonin (a neurohormone) synthesis* [6]

Substrate for serotonin synthesis* [7,8]

Substrate for melatonin synthesis* [9]

Supports sleep* [1,10–17]

Supports social cognition*

Promotes social behaviors* [18,19]

Supports prosocial interactions* [19–24]

Promotes charitable behaviors* [25]

Supports healthy mood*

Supports emotional processing and mental energy* [26]

Supports a positive mental-emotional bias* [12,27–29]

Supports a calm mood* [12,27,30]

Supports healthy functional connectivity between the default mode network and emotion-related brain regions* [31]

Promotes exercise performance* 

Supports power output* [32,33]

Delays time to exertion* [32,33] 

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1]E. Hartmann, C.L. Spinweber, J. Nerv. Ment. Dis. 167 (1979) 497–499.

[2]A.A.-B. Badawy, Int. J. Tryptophan Res. 10 (2017) 1178646917691938.

[3]G. Magni, A. Amici, M. Emanuelli, G. Orsomando, N. Raffaelli, S. Ruggieri, Cell. Mol. Life Sci. 61 (2004) 19–34.

[4]W. Ying, Antioxid. Redox Signal. 10 (2008) 179–206.

[5]D.S. Riddick, X. Ding, C.R. Wolf, T.D. Porter, A.V. Pandey, Q.-Y. Zhang, J. Gu, R.D. Finn, S. Ronseaux, L.A. McLaughlin, C.J. Henderson, L. Zou, C.E. Flück, Drug Metab. Dispos. 41 (2013) 12–23.

[6]L. Palego, L. Betti, A. Rossi, G. Giannaccini, J. Amino Acids 2016 (2016) 8952520.

[7]J.D. Fernstrom, Physiol. Rev. 63 (1983) 484–546.

[8]J.D. Fernstrom, J. Nutr. Biochem. 1 (1990) 508–517.

[9]S. Esteban, C. Nicolaus, A. Garmundi, R.V. Rial, A.B. Rodríguez, E. Ortega, C.B. Ibars, Mol. Cell. Biochem. 267 (2004) 39–46.

[10]R.J. Wyatt, K. Engelman, D.J. Kupfer, D.H. Fram, A. Sjoerdsma, F. Snyder, Lancet 2 (1970) 842–846.

[11]C.F. George, T.W. Millar, P.J. Hanly, M.H. Kryger, Sleep 12 (1989) 345–353.

[12]R. Bravo, S. Matito, J. Cubero, S.D. Paredes, L. Franco, M. Rivero, A.B. Rodríguez, C. Barriga, Age 35 (2013) 1277–1285.

[13]A.N. Nicholson, B.M. Stone, Electroencephalogr. Clin. Neurophysiol. 47 (1979) 539–545.

[14]H.S. Schmidt, Bull. Eur. Physiopathol. Respir. 19 (1983) 625–629.

[15]C. Hudson, S.P. Hudson, T. Hecht, J. MacKenzie, Nutr. Neurosci. 8 (2005) 121–127.

[16]J.G. Lindsley, E.L. Hartmann, W. Mitchell, Sleep 6 (1983) 247–256.

[17]K. Demisch, J. Bauer, K. Georgi, Pharmacopsychiatry 20 (1987) 245–248.

[18]L. Steenbergen, B.J. Jongkees, R. Sellaro, L.S. Colzato, Neurosci. Biobehav. Rev. 64 (2016) 346–358.

[19]S.N. Young, Philos. Trans. R. Soc. Lond. B Biol. Sci. 368 (2013) 20110375.

[20]D.S. Moskowitz, G. Pinard, D.C. Zuroff, L. Annable, S.N. Young, Neuropsychopharmacology 25 (2001) 277–289.

[21]A. Nantel-Vivier, R.O. Pihl, S.N. Young, S. Parent, S.A. Bélanger, R. Sutton, M.-E. Dubois, R.E. Tremblay, J.R. Séguin, PLoS One 6 (2011) e20304.

[22]K. Hogenelst, R.A. Schoevers, M. Aan Het Rot, Int. J. Neuropsychopharmacol. 18 (2015).

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[25]L. Steenbergen, R. Sellaro, L.S. Colzato, Front. Psychol. 5 (2014) 1451.

[26]M.H. Mohajeri, J. Wittwer, K. Vargas, E. Hogan, A. Holmes, P.J. Rogers, R. Goralczyk, E.L. Gibson, Br. J. Nutr. 113 (2015) 350–365.

[27]G. Lindseth, B. Helland, J. Caspers, Arch. Psychiatr. Nurs. 29 (2015) 102–107.

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[31]Y.I. Deza‐Araujo, P.T. Neukam, M. Marxen, D.K. Müller, T. Henle, M.N. Smolka, Hum. Brain Mapp. 40 (2019) 1844–1855.

[32]C. Javierre, R. Segura, J.L. Ventura, A. Suárez, J.M. Rosés, Int. J. Neurosci. 120 (2010) 319–327.

[33]R. Segura, J.L. Ventura, Int. J. Sports Med. 9 (1988) 301–305.

N-Acetyl L-Tyrosine

Scientific Name:
(2S)-2-(acetylamino)-3-(4-hydroxyphenyl)propanoic acid

Betaine

Betaine was originally found in sugar beets (Beta vulgaris), which is the source of its name. Betaines are a group of structurally similar compounds. But because the first betaine discovered was trimethylglycine (the type of betaine found in sugar beets), betaine is commonly used as a synonym for trimethylglycine (TMG), though TMG is more specifically called glycine betaine (there can be non-glycine containing betaines but they are not typically used as dietary supplements). Betaine is an amino acid derivative (i.e., it falls into the protein category). It is found in some foods—in addition to beet roots, other good sources include quinoa, spinach, lamb and wheat brain. Betaine can also be made in the body from choline. This is thought to be a main metabolic fate of dietary choline. However, according to the National Institute of Health most adults don’t get the recommended amount of choline in their diet, so relying on choline (which is also needed to produce phosphatidylcholine for cell membranes and the neurotransmitter acetylcholine) to make betaine can be akin to the saying “Robbing Peter to pay Paul.” Betaine is an important cofactor in methylation, a process that occurs in cells where methyl groups (-CH3) are donated for other processes in the body. These processes include (1) synthesizing neurotransmitters such as dopamine and serotonin, (2) making melatonin and CoQ10, (3) methylation of DNA for epigenetics, (4) remethylation of homocysteine [1] (which has a key role in cardiovascular health [2]), and (5) influencing S-Adenosyl Methionine (SAMe) and folate levels (since they are actively involved in methylation). Betaine is thought to be the source of up to 60% of the methyl groups required for the methylation of homocysteine [3]. Strategies that boost NAD can decrease betaine [4,5] (NAD metabolites are methylated for elimination). Because of this, experts recommend supplementing betaine when strategies are used to boost NAD. Betaine has been largely used to support heart and liver function, but more recently has been receiving attention as a possible ergogenic (i.e., sports performance) and nootropic. Some biohackers use betaine to support sleep.*

TOP BENEFITS OF BETAINE

Supports NAD metabolism *

Supports aspects of sports performance *

Supports brain health *

QUALIA’S BETAINE SOURCING

Betaine sourcing is focused on ensuring it is Non-GMO, gluten-free, and vegan.

BETAINE FORMULATING PRINCIPLES AND RATIONALE

Betaine plays a central role in methylation and is involved in the synthesis of important neurotransmitters (dopamine and serotonin) and the neurohormone melatonin. It is also something that can be decreased when higher amounts of niacin equivalent compounds are supplemented. For these reasons, it can play a role in a variety of different types of formulations. The amount of betaine used in a formulation will vary depending upon the purpose it is being used for. In general, Qualia believes it’s prudent to supplement betaine (or a choline source) when niacin equivalents are used in amounts significantly greater than the daily value (DV) to ensure against unintended depletion. When used to ensure against depletion a general rule of thumb is that approximately 1 mg of betaine can be used for each mg of niacin equivalent supplemented. When used for supporting homocysteine metabolism, heart or liver health, as a nootropic or ergogenic (i.e., not simply to ensure against depletion), or for supporting sleep, higher amounts may be used. Servings above 1500 mg a day may increase cholesterol levels, so, even in these other applications, Qualia believes in using a more moderate serving of betaine, combined with other supportive nutrients.* 

BETAINE KEY MECHANISMS

Supports homocysteine metabolism*

Methylates homocysteine to produce the amino acid L-methionine* [1]

Modulates the blood levels of homocysteine* [6–8]

Supports NAD metabolome*

Supports the demand for methyl groups caused by the metabolism of niacin equivalents (e.g., niacin, niacinamide, nicotinamide riboside, NMN)* [9]

Supports the production of hepatic S-adenosylmethionine* [10–12]

Balances the reduction in hepatic levels of S-adenosylmethionine (SAMe) caused by the metabolism of niacin equivalents* [9]

Supports mitochondrial function and structure*

Supports mitochondrial structure* [13,14]

Supports mitochondrial function* [15–17]

Supports electron transport chain and oxidative phosphorylation performance* [15,16,18,19]

Supports fatty acid oxidation* [13,20]

Supports brain function*

Supports memory* [21–25]

Supports betaine-GABA transporters* [24,25]

Supports neuronal mitochondrial performance* [19]

Supports brain phospholipid metabolism* [20]

Supports brain antioxidant defenses* [23,25–27]

Supports healthy liver function*

Supports hepatic fatty acid metabolism* [10–13,18,28]

Supports liver antioxidant defenses* [15,17]

Supports exercise performance*

Supports resistance training performance* [29–33]

Supports anabolic signaling* [34]

Supports healthy gastrointestinal function*

Supports a healthy gut microbiota composition* [35–39] 

Supports cell function*

Osmolyte—regulates cell hydration* [40]

Complementary ingredients*

Choline—Supplementation with choline sources can support betaine levels* [41,42]  

S-Adenosyl Methionine (SAMe)—Supplementation with betaine can support SAMe levels* [43]

Folic acid in regulating homocysteine levels* [7]

Melatonin for gut health* [44,45]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

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[6]M.R. Olthof, T. van Vliet, E. Boelsma, P. Verhoef, J. Nutr. 133 (2003) 4135–4138.

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[10]A.J. Barak, H.C. Beckenhauer, M. Junnila, D.J. Tuma, Alcohol. Clin. Exp. Res. 17 (1993) 552–555.

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[12]S. Mukherjee, TOTRANSMJ 3 (2011) 1–4.

[13]L. Zhang, Y. Qi, Z. ALuo, S. Liu, Z. Zhang, L. Zhou, Food Funct. 10 (2019) 216–223.

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[18]K.K. Kharbanda, S.L. Todero, A.L. King, N.A. Osna, B.L. McVicker, D.J. Tuma, J.L. Wisecarver, S.M. Bailey, Int. J. Hepatol. 2012 (2012) 962183.

[19]N.K. Singhal, S. Li, E. Arning, K. Alkhayer, R. Clements, Z. Sarcyk, R.S. Dassanayake, N.E. Brasch, E.J. Freeman, T. Bottiglieri, J. McDonough, J. Neurosci. 35 (2015) 15170–15186.

[20]N. Abu Ahmad, M. Raizman, N. Weizmann, B. Wasek, E. Arning, T. Bottiglieri, O. Tirosh, A.M. Troen, FASEB J. 33 (2019) 9334–9349.

[21]K. Kunisawa, K. Kido, N. Nakashima, T. Matsukura, T. Nabeshima, M. Hiramatsu, Eur. J. Pharmacol. 796 (2017) 122–130.

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[32]E.C. Lee, C.M. Maresh, W.J. Kraemer, L.M. Yamamoto, D.L. Hatfield, B.L. Bailey, L.E. Armstrong, J.S. Volek, B.P. McDermott, S.A. Craig, J. Int. Soc. Sports Nutr. 7 (2010) 27.

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[34]J.M. Apicella, E.C. Lee, B.L. Bailey, C. Saenz, J.M. Anderson, S.A.S. Craig, W.J. Kraemer, J.S. Volek, C.M. Maresh, Eur. J. Appl. Physiol. 113 (2013) 793–802.

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[44]M.R. Werbach, Altern. Ther. Health Med. 14 (2008) 54–58.

[45]R. de S. Pereira, J. Pineal Res. 41 (2006) 195–200.

L-Cystine

L-cystine is the chief sulfur-containing compound in protein. It is found in eggs, meat, dairy products, and whole grain foods. L-cystine is the disulfide form of L-cysteine, which means it consists of two molecules of L-cysteine—this is why it is occasionally referred to as dicysteine—bonded together at their sulfur groups.  Inside cells, L-cystine is metabolized into L-cysteine, which, along with glutamine and glycine, is used to make an important detoxification and antioxidant molecule called “glutathione”[1]. L-cysteine availability limits the rate of glutathione production (it is thought to be rate-limiting) [1]. Supplying L-cystine allows the body to restore intracellular glutathione levels when demand has been increased or under circumstances when it is lower (such as older age or increased toxin exposure) in tissues throughout the body (including the brain, liver, and muscles). L-cystine promotes glutathione-related antioxidant defenses, which helps protect cells and mitochondria against free radicals, cell membrane damage, damage from metals and toxins, and other oxidative stress-related and aging issues. L-cystine plays important structure and function roles in immune cells, skeletal muscle, and connective tissue. Hair and skin contain approximately 10–14% cystine by mass.*

TOP BENEFITS OF L-CYSTINE

Supports the production of glutathione *

Supports antioxidant defenses *

Supports healthy immune responses *

QUALIA’S L-CYSTINE SOURCING

L-Cystine is non-GMO and gluten-free.

L-CYSTINE FORMULATING PRINCIPLES AND RATIONALE

Average dietary intake of L-cystine has been estimated to be about 1000 mg/day [2]. L-cysteine is generally considered to be dose-dependent (see Qualia Dosing Principles) in the range it’s most commonly used (between 70-700 mg a day). Our main goal with L-cystine is to augment the supply of dietary precursors to make glutathione, rather than to try to fully replace average L-cystine intake. Because we use L-cystine in combination with other ingredients with which it may have complementary effects, we opted to use a serving at the lower end of the supplemental range.*

L-CYSTINE KEY MECHANISMS

Supports antioxidant defenses*

Supports glutathione levels* [3–5]

Supports healthy mitochondrial ROS production* [6]

Support brain glutathione levels* [7]

Supports neuroprotection (secondary to boosting glutathione and antioxidant defenses)* [7–10]

Supports gut glutathione levels* [11]

Supports healthy immune system function*

Supports general immune health* [3,12–15]

Supports post-exercise immunity* [13,14,16]

Supports innate immunity* [13,14,16]

Supports adaptive immunity* [3,13,16,17]

Supports healthy  immune signaling* [3–5,17,18]

Supports healthy immune cell function* [13,14,16,17]

Supports healthy antibody responses* [3,17]

Supports T cell glutathione production* [19]

Supports gut immune signaling and barrier function* [11,20]

Complementary ingredients*

L-Theanine in support of general immune health* [3,12–17,21]

Glycine in support of glutathione synthesis* [22,23]

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

REFERENCES

[1]S.C. Lu, Biochim. Biophys. Acta 1830 (2013) 3143–3153.

[2]Institute of Medicine, Food and Nutrition Board, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Subcommittee on Interpretation and Uses of Dietary Reference Intakes, Subcommittee on Upper Reference Levels of Nutrients, Panel on the Definition of Dietary Fiber, Panel on Macronutrients, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids, National Academies Press, 2005.

[3]Y. Takagi, S. Kurihara, N. Higashi, S. Morikawa, T. Kase, A. Maeda, H. Arisaka, S. Shibahara, Y. Akiyama, J. Vet. Med. Sci. advpub (2010) 0911170039–0911170039.

[4]T. Shibakusa, T. Mikami, S. Kurihara, Y. Chiba, T. Tsuchiya, T. Miyachi, A. Oyama, K.A.K. Tanaka, N. Koyama, Clin. Nutr. 31 (2012) 555–561.

[5]T. Miyakuni, K. Fukatsu, M. Ri, S. Murakoshi, Y. Inoue, S. Kurihara, T. Takayama, H. Yasuhara, Ann. Nutr. Metab. 73 (2018) 131–137.

[6]A. Gomez, J. Gomez, M. Lopez Torres, A. Naudi, N. Mota-Martorell, R. Pamplona, G. Barja, J. Bioenerg. Biomembr. 47 (2015) 199–208.

[7]E. Ignowski, A.N. Winter, N. Duval, H. Fleming, T. Wallace, E. Manning, L. Koza, K. Huber, N.J. Serkova, D.A. Linseman, Free Radic. Biol. Med. 124 (2018) 328–341.

[8]A.N. Winter, E.K. Ross, V. Daliparthi, W.A. Sumner, D.M. Kirchhof, E. Manning, H.M. Wilkins, D.A. Linseman, Oxid. Med. Cell. Longev. 2017 (2017) 3103272.

[9]C. Liapi, A. Zarros, S. Theocharis, K. Voumvourakis, F. Anifantaki, E. Gkrouzman, Z. Mellios, N. Skandali, H. Al-Humadi, S. Tsakiris, Biol. Trace Elem. Res. 143 (2011) 1673–1681.

[10]C. Liapi, A. Zarros, S. Theocharis, H. Al-Humadi, F. Anifantaki, E. Gkrouzman, Z. Mellios, N. Skandali, S. Tsakiris, Biometals 22 (2009) 329–335.

[11]M.T.J. van Ampting, A.J. Schonewille, C. Vink, R.J.M. Brummer, R. van der Meer, I.M.J. Bovee-Oudenhoven, BMC Physiol. 9 (2009) 6.

[12]K. Miyagawa, Y. Hayashi, S. Kurihara, A. Maeda, Geriatr. Gerontol. Int. 8 (2008) 243–250.

[13]S. Murakami, S. Kurihara, N. Koikawa, A. Nakamura, K. Aoki, H. Yosigi, K. Sawaki, M. Ohtani, Biosci. Biotechnol. Biochem. 73 (2009) 817–821.

[14]S. Kawada, K. Kobayashi, M. Ohtani, C. Fukusaki, J. Strength Cond. Res. 24 (2010) 846–851.

[15]S. Kurihara, T. Hiraoka, M. Akutsu, E. Sukegawa, M. Bannai, S. Shibahara, J. Amino Acids 2010 (2010) 307475.

[16]S. Murakami, S. Kurihara, C.A. Titchenal, M. Ohtani, J. Int. Soc. Sports Nutr. 7 (2010) 23.

[17]S. Kurihara, S. Shibahara, H. Arisaka, Y. Akiyama, J. Vet. Med. Sci. 69 (2007) 1263–1270.

[18]K.A.K. Tanaka, S. Kurihara, T. Shibakusa, Y. Chiba, T. Mikami, Clin. Nutr. 34 (2015) 1159–1165.

[19]T.B. Levring, M. Kongsbak, A.K.O. Rode, A. Woetmann, N. Ødum, C.M. Bonefeld, C. Geisler, Oncotarget 6 (2015) 21853–21864.

[20]C.J. Kim, J. Kovacs-Nolan, C. Yang, T. Archbold, M.Z. Fan, Y. Mine, Biochim. Biophys. Acta 1790 (2009) 1161–1169.

[21]S. Kurihara, T. Shibakusa, K.A. Tanaka, Springerplus 2 (2013) 635.

[22]R.V. Sekhar, S.G. Patel, A.P. Guthikonda, M. Reid, A. Balasubramanyam, G.E. Taffet, F. Jahoor, Am. J. Clin. Nutr. 94 (2011) 847–853.

[23]D. Nguyen, J.W. Hsu, F. Jahoor, J Clin Endocrinol Metab 99 (2014) 169–177.